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Cisplatin-induced nephrotoxicity in childhood cancer: comparison between two countries

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Abstract

Background

Various definitions used to describe cisplatin nephrotoxicity potentially lead to differences in determination of risk factors. This study evaluated incidence of kidney injury according to commonly used and alternative definitions in two cohorts of children who received cisplatin.

Methods

This retrospective cohort study included children from Vancouver, Canada (one center), and Mexico City, Mexico (two centers), treated with cisplatin for a variety of solid tumors. Serum creatinine–based definitions (KDIGO and Pediatric RIFLE (pRIFLE)), electrolyte abnormalities consisted of hypokalemia, hypophosphatemia and hypomagnesemia (based on NCI-CTCAE v5), and an alternative definition (Alt-AKI) were used to describe nephrotoxicity. Incidence with different definitions, definitional overlap, and inter-definition reliability was analyzed.

Results

In total, 173 children (100 from Vancouver, 73 from Mexico) were included. In the combined cohort, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity compared to pRIFLE and KDIGO criteria (82.7 vs. 63.6 vs. 44.5%, respectively). Nephrotoxicity and all electrolyte abnormalities were significantly more common in Vancouver cohort than in Mexico City cohort except when using KDIGO definition. The most common electrolyte abnormalities were hypomagnesemia (88.9%, Vancouver) and hypophosphatemia (24.2%, Mexico City). The KDIGO definition provided highest overlap of cases in Vancouver (100%), Mexico (98.6%), and the combined cohort (99.4%). Moderate overall agreement was found among Alt-AKI, KDIGO, and pRIFLE definitions (κ = 0.18, 95% CI 0.1–0.27) in which KDIGO and pRIFLE showed moderate agreement (κ = 0.48, 95% CI 0.36–0.60).

Conclusions

Compared to pRIFLE and KDIGO criteria, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity. pRIFLE is more sensitive to detect not only actual kidney injury but also patients at risk of cisplatin nephrotoxicity, while KDIGO seems more useful to detect clinically significant kidney injury.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We gratefully acknowledge the participation of all patients and families who took part in this study. We also acknowledge the contributions of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) Consortium and Mexican Cooperative Oncology Network (MexiCON).

Funding

This research was funded by Indonesia Endowment Fund for Education (LPDP) Ministry of Finance, the Republic of Indonesia (as a part of ZZ’s Ph.D. project, grant no. 20161022049506). The APC was funded by Indonesia Endowment Fund for Education (LPDP). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

Author notes

  1. A.H. Maitland-van der Zee and B.C. Carleton contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, UMC Location University of Amsterdam, Amsterdam, The Netherlands

    Zulfan Zazuli, Susanne J. H. Vijverberg & Anke H. Maitland-van der Zee

  2. Department of Pharmacology-Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia

    Zulfan Zazuli

  3. Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Catharina J. P. Op ’t Hoog & Rosalinde Masereeuw

  4. British Columbia Children’s Hospital, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada

    Shahrad Rod Rassekh

  5. Hospital Infantil de México Federico Gómez, Ciudad de Mexico, México

    Mara Medeiros

  6. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, México

    Mara Medeiros

  7. Centro de Adiestramiento en Investigación Clínica, Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico

    Rodolfo Rivas-Ruiz

  8. BC Children’s Hospital Research Institute, Vancouver, BC, Canada

    Bruce C. Carleton

  9. Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Bruce C. Carleton

  10. Pharmaceutical Outcomes Program, British Columbia Children’s Hospital, Vancouver, BC, Canada

    Bruce C. Carleton

Authors
  1. Zulfan Zazuli
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  2. Catharina J. P. Op ’t Hoog
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  9. Bruce C. Carleton
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Contributions

Conceptualization: ZZ, SV, AHM, and BC; methodology: ZZ, SV, AHM, and BC; validation: ZZ and COH; formal analysis: ZZ and COH; investigation: ZZ and COH; resources: BC and MM; data curation: SRR, MM, RR, and BC; writing—original draft preparation: ZZ; writing—review and editing: ZZ, COH, SV, RM, SRR, MM, RR, AHM, and BC; visualization: ZZ; supervision: SV, RM, AHM, and BC; project administration: ZZ and COH; funding acquisition: ZZ, BC, and MM.

Corresponding author

Correspondence to Bruce C. Carleton.

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Zazuli, Z., Op ’t Hoog, C.J.P., Vijverberg, S.J.H. et al. Cisplatin-induced nephrotoxicity in childhood cancer: comparison between two countries. Pediatr Nephrol 38, 593–604 (2023). https://doi.org/10.1007/s00467-022-05632-z

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